Association analysis of common variants in FOXO3 with type 2 diabetes in a South Indian Dravidian population

Nair, Anup K.; Sugunan, Divya; Kumar, Harish; Gopalakrishnapillai, Anilkumar

doi:10.1016/j.gene.2011.09.032

Cited by 9 publications

(11 citation statements)

References 41 publications

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“…Improved insulin sensitivity has been considered as a feature of long-lived individuals. However, a previous study found no associations between FOXO3A SNPs (rs2802288, rs1935949, rs9372190, rs2883881, rs2764264, rs13217795, rs9480867 and rs3800227) and type 2 diabetes and related parameters, suggesting that these SNPs influence longevity via an entirely different mechanism 26. These findings indicate that different FOXO3A polymorphisms may affect human longevity through different mechanisms.…”

Section: Discussionmentioning

confidence: 73%

Association between FOXO3A gene polymorphisms and human longevity: a meta-analysis

et al. 2014

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Numerous studies have shown associations between the FOXO3A gene, encoding the forkhead box O3 transcription factor, and human or specifically male longevity. However, the associations of specific FOXO3A polymorphisms with longevity remain inconclusive. We performed a meta-analysis of existing studies to clarify these potential associations. A comprehensive search was conducted to identify studies of FOXO3A gene polymorphisms and longevity. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by comparing the minor and major alleles. A total of seven articles reporting associations of FOXO3A polymorphisms with longevity were identified and included in this meta-analysis. These comprised 11 independent studies with 5241 cases and 5724 controls from different ethnic groups. rs2802292, rs2764264, rs13217795, rs1935949 and rs2802288 polymorphisms were associated with human longevity (OR = 1.36, 95% CI = 1.10–1.69, P = 0.005; OR = 1.20, 95% CI = 1.04–1.37, P = 0.01; OR = 1.27, 95% CI = 1.10–1.46, P = 0.001; OR = 1.14, 95% CI = 1.01–1.27 and OR = 1.24, 95% CI = 1.07–1.43, P = 0.003, respectively). Analysis stratified by gender indicated significant associations between rs2802292, rs2764264 and rs13217795 and male longevity (OR = 1.54, 95% CI = 1.33–1.79, P < 0.001; OR = 1.38, 95% CI = 1.15–1.66, P = 0.001; and OR = 1.39, 95% CI = 1.15–1.67, P = 0.001), but rs2802292, rs2764264 and rs1935949 were not linked to female longevity. Moreover, our study showed no association between rs2153960, rs7762395 or rs13220810 polymorphisms and longevity. In conclusion, this meta-analysis indicates a significant association of five FOXO3A gene polymorphisms with longevity, with the effects of rs2802292 and rs2764264 being male-specific. Further investigations are required to confirm these findings.

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Section: Discussionmentioning

confidence: 73%

Association between FOXO3A gene polymorphisms and human longevity: a meta-analysis

et al. 2014

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“…This research showed a positive association between FOXO3 rs2802292 and 4 other SNPs of this gene with phenotypes shown to predict survival in a combined sample of male and female oldest-old individuals. No association between FOXO3 and type 2 diabetes was found in an elderly Indian population study, which included a sample of 994 type 2 diabetic individuals and 984 normoglycemic controls ( Nair et al. , 2012 ).…”

Section: Discussionmentioning

confidence: 98%

An association study of FOXO3 variant and longevity

et al. 2018

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Human longevity is a polygenic and multifactorial trait. Pathways related to lifespan are complex and involve molecular, cellular, and environmental processes. In this analytical observational study, we evaluated the relationship between environment factors, oxidative stress status, DNA integrity level, and the association of FOXO3 (rs2802292), SOD2 (rs4880), APOE (rs429358 and rs7412), and SIRT1 (rs2273773) polymorphisms with longevity in oldest-old individuals from southeastern Brazil. We found an association between the FOXO3 GG genotype and gender. While lifestyle, anthropometric, and biochemical characteristics showed significant results, DNA damage and oxidative stress were not related to lifespan. We found that long-lived individuals with FOXO3 GT genotype had low levels of triglycerides. This study is the first to demonstrate that FOXO3 could be a candidate gene for longevity in the Brazilian population. These results are important in terms of provisions of health care for age-related diseases and lifespan, and provide insight for further research on epigenetic, gene regulation, and expression in oldest-old individuals.

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“…Similarly, in a middle-aged South Indian Dravidian population, Nair et al. found that the carriers of rs2802288*A also seemed to have lower FPG and BMI, indicating a better status of insulin resistance21. In a small Danish twin cohort, rs2802292*G was found to be associated with enhanced peripheral and hepatic insulin sensitivity, mediated by the increased skeletal muscle- FOXO3 expression20.…”

Section: Discussionmentioning

confidence: 92%

FOXO3 variants are beneficial for longevity in Southern Chinese living in the Red River Basin: A case-control study and meta-analysis

Sun

Zheng

et al. 2015

Sci Rep

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Forkhead box class O (FOXO) transcription factors play a crucial role in longevity across species. Several polymorphisms in FOXO3 were previously reported to be associated with human longevity. However, only one Chinese replication study has been performed so far. To verify the role of FOXO3 in southern Chinese in the Red River Basin, a community-based case-control study was conducted, and seven polymorphisms were genotyped in 1336 participants, followed by a meta-analysis of eight case-control studies that included 5327 longevity cases and 4608 controls. In our case-control study, we found rs2802288*A and rs2802292*G were beneficial to longevity after Bonferroni correction (pallele = 0.005, OR = 1.266; pallele = 0.026, OR = 1.207). In addition, in the longevity group, carriers with rs2802288*A and rs2802292*G presented reduced HbA1c (p = 0.001), and homozygotes of rs2802292*GG presented improved HOMA–IR (p = 0.014). The meta-analysis further revealed the overall contribution of rs2802288*A and rs2802292*G to longevity. However, our stratified analysis revealed that rs2802292*G might act more strongly in Asians than Europeans, for enhancement of longevity. In conclusion, our study provides convincing evidence for a significant association between the rs2802288*A and rs2802292*G gene variants in FOXO3 and human longevity, and adds the Southern Chinese in the Red River Basin to the growing number of human replication populations.

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Association analysis of common variants in FOXO3 with type 2 diabetes in a South Indian Dravidian population

Cited by 9 publications

References 41 publications

Association between FOXO3A gene polymorphisms and human longevity: a meta-analysis

Association between FOXO3A gene polymorphisms and human longevity: a meta-analysis

An association study of FOXO3 variant and longevity

FOXO3 variants are beneficial for longevity in Southern Chinese living in the Red River Basin: A case-control study and meta-analysis

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